The Agricultural Health Study (AHS) is a major effort which is designed to evaluate the relationship between pesticides and other agricultural factors and the risk of cancer and other diseases. Enrollment in this study includes about 90,000 men and women from Iowa and North Carolina. From 1993-1997 detailed information was obtained by self-administered questionnaire and from 1998 through September 2003 and again from 2004 through 2010 computer assisted telephone interviews have updated the information collected at enrollment. Telephone interviews include questions on pesticides used and other agricultural exposures, lifestyle factors, medical and family history of disease, and diet. A new question is currently being administered (2010-2015) which is focusing on chronic disease other than cancer, this effort is being led by investigators from NIEHS. We are also collecting buccal cell samples as a source of genomic DNA for GXE studies and studies of epigenetic mechanisms. Analyses on cancer incidence and other chronic diseases is continuing and a number of manuscripts focusing on cancer incidence overall, prostate cancer, colorectal cancer, pancreatic cancer, lunch cancer, breast cancer, and melanoma are now published. Analysis of NHL and leukemia is now underway. Findings from the prostate cancer analysis suggest a number of pesticides are associated with a prostate cancer risk. The risk of prostate cancer is particularly strong among those with a family history of prostate cancer. The Agricultural Health Study has also analyzed the cancer experience of pesticide applicators that have used chlorpyrifos, alachlor, atrazine, glyphosate, malathion, metoachlor, dicamba, fonofos, phorate and a number of other pesticides of wide-spread use and toxicologic interest. A biomarker study [The Corn Farmer Study], nested within the AHS is assessing perturbations in the immune system of a group of Iowa corn farmers and a control group not exposed to corn farming, during a calendar year, some result have been published in 2014. A nested molecular case-control study of prostate cancer began in 2007 and GXE results have now been published on six genetic pathways and epigenetic results are expected in 2015. A cross-sectional study of pesticides and MGUS (a precursor of multiple myeloma) was published in 2009 showing AHS cohort members to be at twice the risk of MGUS compared to the general population. As a result of this investigation a new study with an anticipated participation of 1, 600 study subjects was initiated in 2010 to identify the exposures responsible for an elevated MGUS frequency. Initial results are expected in 2015. Another nested study is collecting dust samples from selected AHS participants' homes for later evaluation of pesticide concentrations and endotoxin levels. Results are expected in 2016. The risk of a high pesticide exposure event (HPEE) resulting in symptoms is more pronounced among farmers whose farms were in poor financial condition compared to those whose farms were not and among those with a lower risk acceptance. HPEE has been associated with neurologic and respiratory symptoms. Several manuscripts with analyses of mechanical injury associated operating farm have been published. Several manuscripts with analysis of respiratory wheeze have been published indicating that diesel tractor use, work in poultry operations and exposure to several pesticides are risk factors for respiratory wheeze. These cross-sectional studies will be follow-up with additional longitudinal analyses from the Lung Health Study in 2011-2015. A study of Parkinson's disease nested within the Agricultural Health Study is now published. Several other projects to evaluate the cancer risk from pesticide exposure are published. Analysis of data from cohort analysis of non-Hodgkin's lymphoma noted several associations with agricultural use of pesticdes is now undergoing peer review. Hodgkin's Lymphoma affects blood levels of organ chlorines, which could result in misclassification of exposure and distort findings. Farmers were found to be at elevated risk for prostate cancer in a study of mortality in 24 states. Contrary to earlier investigations, however, the risk of breast cancer was not associated with serum levels of DDT among women in Mexico City. A methodological study to compare pesticide levels in dust samples from vacuum cleaner bags, which is a simpler and less expensive approach than the HVSS, provides a reliable indication of pesticide levels on dust in homes. Several feasibility studies have been conducted among migrant and seasonal farm workers to determine appropriate methods for epidemiologic investigations in this understudied group. Results from this effort appear in a special volume of the American Journal of Industrial Medicine in the near future. A review of the literature was conducted which suggested that pesticides may play a role in the development of childhood and adult cancers. Case-control studies of cancers of the brain and stomach in Nebraska provide an opportunity to assess the role of agricultural, general environmental, and lifestyle factors in the development of these tumors. Blood and urine have been collected from 30 applicators applying the herbicide 2, 4-D to relate dose to possible biologic effects, and dose-response gradient was found for 2,4-D and mitotic index. In a separate study, results suggest that farm exposures are more strongly associated with NHL with a (14, 18) translocation than other types of NHL. In yet another study, results suggest that maternal occupational exposure to agricultural chemicals may increase the risk of giving birth to a child with limb defects.